DynaMed EBM Focus 13: In Colorectal Cancer Screening, Multitarget Stool DNA Test Appears to Have Higher Sensitivity Than Fecal Immunochemical Test

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Credits

Physicians: .25 AMA PRA Category I Credits^TM

Family Physicians: .25 Prescribed credits

Nurse Practitioners: .25 Contact hours

Release Date: March 26, 2014

Expiration Date: March 26, 2015

Estimated Completion Time: 15 minutes

There is no fee for this activity.

To Receive Credit

In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon at the end of the article.

Program Overview

Learning Objectives

Upon successful completion of this educational program, the reader should be able to:
1. Discuss the significance of this article as it relates to your clinical practice.
2. Be able to apply this knowledge to your patient's diagnosis, treatment and management.

Faculty Information

Alan Ehrlich, MD - Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA

Michael Fleming, MD, FAAFP - Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company

Disclosures

Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

No commercial support has been received for this activity.

Accreditation Statements

ACCME: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Antidote EducationCompany and EBSCO Publishing. Antidote is accredited by the ACCME to provide continuing medical education for physicians. Antidote Education Company designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 Credits^TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

AAFP: Enduring Material activity, DynaMed EBM Focus, has been reviewed and is acceptable for up to 13 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 7, 2012. Term of approval is for one year from this date with the option of yearly renewal. Each EBM Focus is worth .25 Prescribed credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AANP: This program is approved for 0.25 contact hour of continuing education by the American Academy of Nurse Practitioners.

Program ID: 1304159T

Last week 738 journal articles were evaluated via DynaMed's Systematic Literature Surveillance and summaries of 293 articles were added to DynaMed content.

Based on criteria for selecting "articles most likely to change clinical practice," one article was selected by the DynaMed Editorial Team.

In Colorectal Cancer Screening, Multitarget Stool DNA Test Appears to Have Higher Sensitivity Than Fecal Immunochemical Test
Reference: N Engl J Med 2014 Mar 19 early online (level 2 [mid-level] evidence)

Colorectal cancer is a major cause of morbidity and mortality in the United States (CA Cancer J Clin 2013 Jan;63(1):11). The American Cancer Society and American Gastroenterological Association recommend screening for colorectal cancer beginning at age 50 years, and list both stool DNA test and fecal immunochemical test as options for detecting cancer (CA Cancer J Clin 2008 May-Jun;58(3):130 full-text). The diagnostic performance of a new stool DNA test was compared to the fecal immunochemical test for detection of colorectal cancer in a recent cohort study of 11,016 asymptomatic persons aged 50-84 years with average risk for colorectal cancer.

All patients had the multitarget DNA test and fecal immunochemical test done from a single stool sample prior to planned routine screening colonoscopy (reference standard). The DNA test consisted of a hemoglobin immunoassay plus quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and beta-actin. Patients with a personal or family history of colorectal cancer or a personal history of colorectal neoplasia, digestive cancer, or inflammatory bowel disease were excluded. A total of 9,989 patients (91%) were analyzed after exclusion of 1,027 with uninterpretable or missing results for any screening test, including problems with collection of the stool sample for the DNA test and technical failure due to insufficient DNA. The cutoffs for a positive result were defined as ≥ 183 on the composite score from a logistic-regression algorithm for the DNA test, and > 100 ng/mL hemoglobin for the fecal immunochemical test.

During colonoscopy, 65 persons (0.7%) were found to have colorectal cancer and 757 persons (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps ≥ 1 cm in greatest dimension). For detection of any colorectal cancer, the multitarget stool DNA test had a sensitivity of 92.3% vs. 73.8% with the fecal immunochemical test (p = 0.002). The corresponding number needed to screen to detect 1 case of colorectal cancer was 166 with the multitarget stool DNA test vs. 208 with the fecal immunochemical test. Similarly, for detection of advanced precancerous lesions, the multitarget stool DNA test had a sensitivity of 42.4% vs. 23.8% with the fecal immunochemical test (p < 0.001). The number needed to screen to detect 1 advanced precancerous lesions was 31 with the multitarget stool DNA test vs. 55 with the fecal immunochemical test. The specificity for no colorectal cancer or advanced precancerous lesion was 86.6% with the multitarget stool DNA test vs. 94.9% (p < 0.001) with the fecal immunochemical test. For detection of either colorectal cancer or advanced precancerous lesions, the multitarget DNA test had a positive predictive value of 23.6% and negative predictive value of 94.7%, and the fecal immunochemical test had positive predictive value of 32.6% and negative predictive value of 93.6%.

These results show that stool DNA testing is associated with significantly higher sensitivity than fecal immunochemical testing for detection of colorectal cancer and advanced precancerous lesions, at the expense of lower specificity. For a screening test for cancer, the higher sensitivity is more important, as long as there are not too many false positives, which appears to be the case here. Although the DNA testing had a higher detection rate for identifying colorectal cancers compared to the immunochemical testing, the greater ability to detect precancerous lesions is at least as significant, since the optimal goal is to prevent cancer. Further studies are required to determine the optimal interval screening duration for stool DNA testing, and to address other practical aspects of testing, such as stool collection and ensuring samples have sufficient DNA. The cost of DNA testing must also be considered, particularly since many individuals who do not currently have routine screening may not have access to this technology. Moreover, randomized trials are needed to determine whether stool DNA testing improves clinical outcomes such as mortality when compared to other screening tests.

For more information see the Colorectal cancer screening topic in DynaMed.

Earn CME Credit for reading this e-Newsletter.
For more information on this educational activity, see the CME sidebar.

Call for Peer Reviews

We are currently seeking subspecialty reviewers for our Patient Education Resource Center (PERC). PERC provides fact sheets and discharge instructions for patients leaving the hospital or emergency room. These hand-outs fulfill the meaningful use requirements for the Medicare & Medicare Services Incentive Programs.

Click here to speak with us about becoming a peer reviewer.

DynaMed Careers

Looking for a change? The DynaMed editorial team is expanding and looking for talented and driven individuals. Visit the links below to learn about these exciting opportunities.

Deputy Editor of Oncology
Section Editor of Specialty Content

Learn more about DynaMed Contribution Opportunities

DynaMed Peer Review
Editorial Policies for Reviewers
Education for Clinicians in Training


Quick Links Share with Colleagues Previous EBM Focus Issues Become a DynaMed Reviewer DynaMed Free Trial Send Comment to Editor Credits Physicians: .25 AMA PRA Category I Credits^TM Family Physicians: .25 Prescribed credits Nurse Practitioners: .25 Contact hours Release Date: March 26, 2014 Expiration Date: March 26, 2015 Estimated Completion Time: 15 minutes There is no fee for this activity. To Receive Credit In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon at the end of the article. Program Overview Learning Objectives Upon successful completion of this educational program, the reader should be able to: 1. Discuss the significance of this article as it relates to your clinical practice. 2. Be able to apply this knowledge to your patient's diagnosis, treatment and management. Faculty Information Alan Ehrlich, MD - Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA Michael Fleming, MD, FAAFP - Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company Disclosures Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. No commercial support has been received for this activity. Accreditation Statements ACCME: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Antidote EducationCompany and EBSCO Publishing. Antidote is accredited by the ACCME to provide continuing medical education for physicians. Antidote Education Company designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 Credits^TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. AAFP: Enduring Material activity, DynaMed EBM Focus, has been reviewed and is acceptable for up to 13 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 7, 2012. Term of approval is for one year from this date with the option of yearly renewal. Each EBM Focus is worth .25 Prescribed credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity. AANP: This program is approved for 0.25 contact hour of continuing education by the American Academy of Nurse Practitioners. Program ID: 1304159T	Last week 738 journal articles were evaluated via DynaMed's Systematic Literature Surveillance and summaries of 293 articles were added to DynaMed content. Based on criteria for selecting "articles most likely to change clinical practice," one article was selected by the DynaMed Editorial Team. In Colorectal Cancer Screening, Multitarget Stool DNA Test Appears to Have Higher Sensitivity Than Fecal Immunochemical Test Reference: N Engl J Med 2014 Mar 19 early online (level 2 [mid-level] evidence) Colorectal cancer is a major cause of morbidity and mortality in the United States (CA Cancer J Clin 2013 Jan;63(1):11). The American Cancer Society and American Gastroenterological Association recommend screening for colorectal cancer beginning at age 50 years, and list both stool DNA test and fecal immunochemical test as options for detecting cancer (CA Cancer J Clin 2008 May-Jun;58(3):130 full-text). The diagnostic performance of a new stool DNA test was compared to the fecal immunochemical test for detection of colorectal cancer in a recent cohort study of 11,016 asymptomatic persons aged 50-84 years with average risk for colorectal cancer. All patients had the multitarget DNA test and fecal immunochemical test done from a single stool sample prior to planned routine screening colonoscopy (reference standard). The DNA test consisted of a hemoglobin immunoassay plus quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and beta-actin. Patients with a personal or family history of colorectal cancer or a personal history of colorectal neoplasia, digestive cancer, or inflammatory bowel disease were excluded. A total of 9,989 patients (91%) were analyzed after exclusion of 1,027 with uninterpretable or missing results for any screening test, including problems with collection of the stool sample for the DNA test and technical failure due to insufficient DNA. The cutoffs for a positive result were defined as ≥ 183 on the composite score from a logistic-regression algorithm for the DNA test, and > 100 ng/mL hemoglobin for the fecal immunochemical test. During colonoscopy, 65 persons (0.7%) were found to have colorectal cancer and 757 persons (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps ≥ 1 cm in greatest dimension). For detection of any colorectal cancer, the multitarget stool DNA test had a sensitivity of 92.3% vs. 73.8% with the fecal immunochemical test (p = 0.002). The corresponding number needed to screen to detect 1 case of colorectal cancer was 166 with the multitarget stool DNA test vs. 208 with the fecal immunochemical test. Similarly, for detection of advanced precancerous lesions, the multitarget stool DNA test had a sensitivity of 42.4% vs. 23.8% with the fecal immunochemical test (p < 0.001). The number needed to screen to detect 1 advanced precancerous lesions was 31 with the multitarget stool DNA test vs. 55 with the fecal immunochemical test. The specificity for no colorectal cancer or advanced precancerous lesion was 86.6% with the multitarget stool DNA test vs. 94.9% (p < 0.001) with the fecal immunochemical test. For detection of either colorectal cancer or advanced precancerous lesions, the multitarget DNA test had a positive predictive value of 23.6% and negative predictive value of 94.7%, and the fecal immunochemical test had positive predictive value of 32.6% and negative predictive value of 93.6%. These results show that stool DNA testing is associated with significantly higher sensitivity than fecal immunochemical testing for detection of colorectal cancer and advanced precancerous lesions, at the expense of lower specificity. For a screening test for cancer, the higher sensitivity is more important, as long as there are not too many false positives, which appears to be the case here. Although the DNA testing had a higher detection rate for identifying colorectal cancers compared to the immunochemical testing, the greater ability to detect precancerous lesions is at least as significant, since the optimal goal is to prevent cancer. Further studies are required to determine the optimal interval screening duration for stool DNA testing, and to address other practical aspects of testing, such as stool collection and ensuring samples have sufficient DNA. The cost of DNA testing must also be considered, particularly since many individuals who do not currently have routine screening may not have access to this technology. Moreover, randomized trials are needed to determine whether stool DNA testing improves clinical outcomes such as mortality when compared to other screening tests. For more information see the Colorectal cancer screening topic in DynaMed. Earn CME Credit for reading this e-Newsletter. For more information on this educational activity, see the CME sidebar. Call for Peer Reviews We are currently seeking subspecialty reviewers for our Patient Education Resource Center (PERC). PERC provides fact sheets and discharge instructions for patients leaving the hospital or emergency room. These hand-outs fulfill the meaningful use requirements for the Medicare & Medicare Services Incentive Programs. Click here to speak with us about becoming a peer reviewer. DynaMed Careers Looking for a change? The DynaMed editorial team is expanding and looking for talented and driven individuals. Visit the links below to learn about these exciting opportunities. Deputy Editor of Oncology Section Editor of Specialty Content Learn more about DynaMed Contribution Opportunities DynaMed Peer Review Editorial Policies for Reviewers Education for Clinicians in Training